261 ENGOT-cx11/GOG 3047/KEYNOTE-A18: phase 3 randomized study of pembrolizumab + chemoradiotherapy for high-risk locally advanced cervical cancer

Introduction/Background*

High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 years. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab may be enhanced by concurrent chemoradiotherapy (CCRT). After the KEYNOTE-158 study, in which pembrolizumab showed durable antitumor activity, pembrolizumab monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/GOG 3047/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo-controlled study evaluating pembrolizumab with CCRT for the treatment of high-risk, locally advanced cervical cancer.

Methodology

Approximately 980 patients with high-risk (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) + CCRT followed by 15 cycles of pembrolizumab 400 mg Q6W or 5 cycles of placebo Q3W + CCRT followed by 15 cycles of placebo Q6W. CCRT includes 5 cycles (optional 6th dose) of cisplatin 40 mg/m² Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 20 cycles of pembrolizumab (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 years) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator and overall survival (OS). Secondary endpoints include PFS by blinded independent central review, PFS at 2 years, OS at 3 years, complete response at 12 weeks, objective response rate, PFS and OS by PD-L1 status, quality of life, and safety. Enrolment began May 2020 and is planned for 193 sites in 30 countries. Klikněte nebo klepněte sem a zadejte text.